is an opportunistic pathogenic yeast and is responsible for candidiasis. It readily colonizes host tissues and implant devices, and forms biofilms, which play an important role in pathogenesis and drug resistance. In this study, the antibiofilm, antihyphal, and antivirulence activities of nepodin, isolated from roots, were investigated against a fluconazole-resistant strain and against polymicrobial-microorganism-biofilm formation. Nepodin effectively inhibited biofilm formation without affecting its planktonic cell growth. Also, -root extract and nepodin both inhibited hyphal growth and cell aggregation of . Interestingly, nepodin also showed antibiofilm activities against , , , and strains and against dual biofilms of and or but not against . Transcriptomic analysis performed by RNA-seq and qRT-PCR showed nepodin repressed the expression of several hypha- and biofilm-related genes (, , , and ) and increased the expression of several transport genes (, , and ), which supported phenotypic changes. Moreover, nepodin reduced virulence in a nematode-infection model and exhibited minimal cytotoxicity against the nematode and an animal cell line. These results demonstrate that nepodin and -root extract might be useful for controlling infections and multispecies biofilms.
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